Person: Wible, Cynthia Gayle
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Wible
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Cynthia Gayle
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Wible, Cynthia Gayle
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Publication Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study(Elsevier BV, 2001) Wible, Cynthia Gayle; Anderson, Jane; Shenton, Martha; Kricun, Ashley; Hirayasu, Yoshio; Tanaka, Shin; Levitt, James; O, Brian F; Kikinis, Ron; Jolesz, Ferenc; McCarley, Robert WilliamThe present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial–temporal lobe regions — two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal–prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.Publication MRI anatomy of schizophrenia(Elsevier BV, 1999) McCarley, Robert William; Wible, Cynthia Gayle; Frumin, Melissa; Hirayasu, Yoshio; Levitt, James; Fischer, Iris A.; Shenton, MarthaStructural magnetic resonance imaging (MRI) data have provided much evidence in support of our current view that schizophrenia is a brain disorder with altered brain structure, and consequently involving more than a simple disturbance in neurotransmission. This review surveys 118 peer–reviewed studies with control group from 1987 to May 1998. Most studies (81%) do not find abnormalities of whole brain/intracranial contents, while lateral ventricle enlargement is reported in 77%, and third ventricle enlargement in 67%. The temporal lobe was the brain parenchymal region with the most consistently documented abnormalities. Volume decreases were found in 62% of 37 studies of whole temporal lobe, and in 81% of 16 studies of the superior temporal gyrus (and in 100% with gray matter separately evaluated). Fully 77% of the 30 studies of the medial temporal lobe reported volume reduction in one or more of its constituent structures (hippocampus, amygdala, parahippocampal gyrus). Despite evidence for frontal lobe functional abnormalities, structural MRI investigations less consistently found abnormalities, with 55% describing volume reduction. It may be that frontal lobe volume changes are small, and near the threshold for MRI detection. The parietal and occipital lobes were much less studied; about half of the studies showed positive findings. Most studies of cortical gray matter (86%) found volume reductions were not diffuse, but more pronounced in certain areas. About two thirds of the studies of subcortical structures of thalamus, corpus callosum and basal ganglia (which tend to increase volume with typical neuroleptics), show positive findings, as do almost all (91%) studies of cavum septi pellucidi (CSP). Most data were consistent with a developmental model, but growing evidence was compatible also with progressive, neurodegenerative features, suggesting a “two– hit” model of schizophrenia, for which a cellular hypothesis is discussed. The relationship of clinical symptoms to MRI findings is reviewed, as is the growing evidence suggesting structural abnormalities differ in affective (bipolar) psychosis and schizophrenia.Publication From Tones in Tinnitus to Sensed Social Interaction in Schizophrenia: How Understanding Cortical Organization Can Inform the Study of Hallucinations and Psychosis(Oxford University Press, 2014) ffytche, Dominic H.; Wible, Cynthia GayleThe content, modality, and perceptual attributes of hallucinations and other psychotic symptoms may be related to neural representation at a single cell and population level in the cerebral cortex. A brief survey of some principles and examples of cortical representation and organization will be presented together with evidence for a correspondence between the neurobiology of brain areas activated at the time of a hallucination and the content of the corresponding hallucinatory and psychotic experiences. Contrasting the hallucinations of schizophrenia with other conditions, we highlight phenomenological aspects of hallucinations that are ignored in clinical practice but carry potentially important information about the brain regions and dysfunctions underlying them. Knowledge of cortical representation and organization are being used to develop animal models of hallucination and to test treatments that are now beginning to translate to the clinical domain.Publication Superior Temporal Gyrus Volume Abnormalities and Thought Disorder in Left-Handed Schizophrenic Men(American Psychiatric Publishing, 1999) Holinger, Dorothy; Shenton, Martha; Wible, Cynthia Gayle; Donnino, Robert; Kikinis, Ron; Jolesz, Ferenc; McCarley, Robert WilliamObjective: Studies of schizophrenia have not clearly defined handedness as a differentiating variable. Moreover, the relationship between thought disorder and anatomical anomalies has not been studied extensively in left-handed schizophrenic men. The twofold purpose of this study was to investigate gray matter volumes in the superior temporal gyrus of the temporal lobe (left and right hemispheres) in left-handed schizophrenic men and left-handed comparison men, in order to determine whether thought disorder in the left-handed schizophrenic men correlated with tissue volume abnormalities. Method: Left-handed male patients (N=8) with DSM-III-R diagnoses of schizophrenia were compared with left-handed comparison men (N=10) matched for age, socioeconomic status, and IQ. Magnetic resonance imaging (MRI) with a 1.5-T magnet was used to obtain scans, which consisted of contiguous 1.5-mm slices of the whole brain. MRI analyses (as previously defined by the authors) included the anterior, posterior, and total superior temporal gyrus in both the left and right hemispheres. Results: There were three significant findings regarding the left-handed schizophrenic men: 1) bilaterally smaller gray matter volumes in the posterior superior temporal gyrus (16% smaller on the right, 15% smaller on the left); 2) a smaller volume on the right side of the total superior temporal gyrus; and 3) a positive correlation between thought disorder and tissue volume in the right anterior superior temporal gyrus. Conclusions: These results suggest that expression of brain pathology differs between left-handed and right-handed schizophrenic men and that the pathology is related to cognitive disturbance.Publication Subgenual Cingulate Cortex Volume in First-Episode Psychosis(American Psychiatric Publishing, 1999) Hirayasu, Yoshio; Shenton, Martha; Salisbury, Dean F.; Soo Kwon, Jun; Wible, Cynthia Gayle; Fischer, Iris A.; Yurgelun-Todd, Deborah; Zarate, Carlos; Kikinis, Ron; Jolesz, Ferenc; McCarley, Robert WilliamObjective: Gray matter volume and glucose utilization have been reported to be reduced in the left subgenual cingulate of subjects with familial bipolar or unipolar depression. It is unclear whether these findings are secondary to recurrent illness or are part of a familial/genetic syndrome. The authors’ goal was to clarify these findings. Method: Volumetric analyses were performed by using magnetic resonance imaging in 41 patients experiencing their first episode of affective disorder or schizophrenia and in 20 normal comparison subjects. Results: The left subgenual cingulate volume of the patients with affective disorder who had a family history of affective disorder was smaller than that of patients with affective disorder with no family history of the illness and the normal comparison subjects. Patients with schizophrenia did not differ from comparison subjects in left subgenual cingulate volume. Conclusions: Left subgenual cingulate abnormalities are present at first hospitalization for psychotic affective disorder in patients who have a family history of affective disorder.Publication An fMRI study of semantic processing in men with schizophrenia(Elsevier BV, 2003) Kubicki, Marek; McCarley, Robert William; Nestor, Paul; Huh, T; Kikinis, Ron; Shenton, Martha; Wible, Cynthia GayleAs a means toward understanding the neural bases of schizophrenic thought disturbance, we examined brain activation patterns in response to semantically and superficially encoded words in patients with schizophrenia. Nine male schizophrenic and 9 male control subjects were tested in a visual levels of processing (LOP) task first outside the magnet and then during the fMRI scanning procedures (using a different set of words). During the experiments visual words were presented under two conditions. Under the deep, semantic encoding condition, subjects made semantic judgments as to whether the words were abstract or concrete. Under the shallow, nonsemantic encoding condition, subjects made perceptual judgments of the font size (uppercase/lowercase) of the presented words. After performance of the behavioral task, a recognition test was used to assess the depth of processing effect, defined as better performance for semantically encoded words than for perceptually encoded words. For the scanned version only, the words for both conditions were repeated in order to assess repetition-priming effects. Reaction times were assessed in both testing scenarios. Both groups showed the expected depth of processing effect for recognition, and control subjects showed the expected increased activation of the left inferior prefrontal cortex (LIPC) under semantic encoding relative to perceptual encoding conditions as well as repetition priming for semantic conditions only. In contrast, schizophrenics showed similar patterns of fMRI activation regardless of condition. Most striking in relation to controls, patients showed decreased LIFC activation concurrent with increased left superior temporal gyrus activation for semantic encoding versus shallow encoding. Furthermore, schizophrenia subjects did not show the repetition priming effect, either behaviorally or as a decrease in LIPC activity. In patients with schizophrenia, LIFC underactivation and left superior temporal gyrus overactivation for semantically encoded words may reflect a disease-related disruption of a distributed frontal temporal network that is engaged in the representation and processing of meaning of words, text, and discourse and which may underlie schizophrenic thought disturbance.Publication Abnormalities of the Left Temporal Lobe and Thought Disorder in Schizophrenia(New England Journal of Medicine (NEJM/MMS), 1992) Shenton, Martha; Kikinis, Ron; Jolesz, Ferenc; Pollak, Seth D.; Lemay, Marjorie; Wible, Cynthia Gayle; Hokama, Hiroto; Martin, John; Metcalf, Dave; Coleman, Michael; McCarley, Robert WilliamBACKGROUND: Data from postmortem, CT, and magnetic resonance imaging (MRI) studies indicate that patients with schizophrenia may have anatomical abnormalities of the left temporal lobe, but it is unclear whether these abnormalities are related to the thought disorder characteristic of schizophrenia. METHODS: We used new MRI neuroimaging techniques to derive (without knowledge of the diagnosis) volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls. RESULTS: As compared with the controls, the patients had significant reductions in the volume of gray matter in the left anterior hippocampus—amygdala (by 19 percent [95 percent confidence interval, 3 to 36 percent]), the left parahippocampal gyrus (by 13 percent [95 percent confidence interval, 3 to 23 percent], vs. 8 percent on the right), and the left superior temporal gyrus (by 15 percent [95 percent confidence interval, 5 to 25 percent]). The volume of the left posterior superior temporal gyrus correlated with the score on the thought-disorder index in the 13 patients evaluated (r = -0.81, P = 0.001). None of these regional volume decreases were accompanied by a decrease in the volume of the overall brain or temporal lobe. The volume of gray matter in a control region (the superior frontal gyrus) was essentially the same in the patients and controls. CONCLUSIONS: Schizophrenia involves localized reductions in the gray matter of the left temporal lobe. The degree of thought disorder is related to the size of the reduction in volume of the left posterior superior temporal gyrus.Publication A Functional Magnetic Resonance Imaging Study of Auditory Mismatch in Schizophrenia(American Psychiatric Publishing, 2001) Wible, Cynthia Gayle; Kubicki, Marek; Yoo, Seung-Schik; Kacher, Daniel F.; Salisbury, Dean F.; Anderson, Mark; Shenton, Martha; Hirayasu, Yoshio; Kikinis, Ron; Jolesz, Ferenc; McCarley, Robert WilliamObjective: Previous research has noted functional and structural temporal lobe abnormalities in schizophrenia that relate to symptoms such as auditory hallucinations and thought disorder. The goal of the study was to determine whether the functional abnormalities are present in schizophrenia at early stages of auditory processing. Method: Functional magnetic resonance imaging activity was examined during the presentation of the mismatch stimuli, which are deviant tones embedded in a series of standard tones. The mismatch stimuli are used to elicit the mismatch negativity, an early auditory event-related potential. Ten patients with schizophrenia and 10 comparison subjects were presented the mismatch stimuli condition and a control condition in which only one tone was presented repeatedly. Results: The superior temporal gyrus showed the most prevalent and consistent activation. The superior temporal gyrus showed less activation in the schizophrenic subjects than in the comparison subjects only during the mismatch stimuli condition. Conclusions: This result is consistent with those of mismatch negativity event-related potential studies and suggests that early auditory processing is abnormal in chronic schizophrenia.Publication Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study(Elsevier BV, 2003) Kubicki, Marek; Westin, Carl-Fredrik; Nestor, Paul; Wible, Cynthia Gayle; Frumin, Melissa; Maier, Stephan; Kikinis, Ron; Jolesz, Ferenc; McCarley, Robert William; Shenton, MarthaBackground: Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia using the new technology of diffusion tensor imaging (DTI). Methods: We used line scan DTI to evaluate diffusion in the CB in 16 male schizophrenia patients and 18 male control subjects, group-matched for age, parental socioeconomic status, and handedness. We acquired 4-mm-thick coronal slices through the entire brain. Maps of fractional anisotropy (FA) were generated to quantify diffusion within the left and right CB on eight slices that included the central portion of the CB. Results: Results showed group differences, bilaterally, in area and mean FA for CB, where patients showed smaller area and less anisotropy than controls. For patients, decreased left CB correlated significantly with attention and working memory measures as assessed by the Wisconsin Card Sorting Test. Conclusions: These data provide strong evidence for CB disruptions in schizophrenia, which may be related to disease-related attention and working memory abnormalities.Publication An MRI study of temporal lobe abnormalities and negative symptoms in chronic schizophrenia(Elsevier BV, 2002) Anderson, Jane E; Wible, Cynthia Gayle; McCarley, Robert William; Jakab, M; Kasai, Kazue; Shenton, MarthaPrevious magnetic resonance imaging (MRI) studies have reported various subtle brain abnormalities in schizophrenic patients, including temporal lobe abnormalities, which are of particular interest given the role of this brain region in auditory and language processing, and the characteristic deficits in these processes in schizophrenia. Subjects in this study were 16 male patients diagnosed with chronic schizophrenia and 15 healthy male comparison subjects. These patients were characterized by negative symptoms. High spatial resolution coronal MRI 1.5-mm-thick slices were used to measure the gray matter volume of the superior temporal gyrus, anterior and posterior amygdala/hippocampal complex, and parahippocampal gyrus. Patients, relative to normal comparison subjects, evinced a reduction of gray matter volume in bilateral superior temporal gyri and anterior amygdala/hippocampal complex. The reduction in gray matter of the superior temporal gyrus in patients with schizophrenia is consistent with previous findings, and is noteworthy in that it was found in this group of patients with predominantly negative symptoms. The reduction in the anterior amygdala/hippocampal complex was an additional temporal lobe finding. These results underscore the role of temporal lobe structures in the pathophysiology of schizophrenia.